Modulation of GABA(A) receptor subunit mRNA levels in olivocerebellar neurons of Purkinje cell degeneration and weaver mutant mice

In olivocerebellar circuits, changes in the subunit composition of GABA(A) receptors occur at a time of extensive synaptic remodeling. In the deep cer ebellar nuclei, GABA(A) receptor alpha(1), beta(2), and gamma(2) subunit mR NA expression increases throughout neonatal development, whereas in the inf erior olivary complex, the perinatal combination of alpha(3), alpha(5), bet a(3), and gamma(2) mRNAs switches to the adult combination of alpha(2), alp ha(4), beta(3), and gamma(1) during postnatal week 2. In situ hybridization was used to examine changes in subunit expression in the olivocerebellar n uclei of Purkinje cell degeneration and weaver mutant mice. In Purkinje cel l degeneration, subunit transcripts decreased below control levels in oliva ry neurons; however, alpha(1), beta(2), and gamma(2) transcript levels were slightly increased in the medial nucleus of the deep cerebellar nuclei. in weaver olivary neurons, although the switch from early- to late-onset subu nit mRNAs occurred as in normal mice, transcript levels were differentially modulated by the mutation. Our studies indicate that major alterations in synaptic connectivity do not prevent developmentally programmed switches in GABA(A) receptor gene expression but can modulate the timing and level of transcript expression in afferent and efferent neurons.